It has been difficult to conclusively identify (much less isolate) ductal cell precursors in the normal pancreas. Consequently, there is a paucity of immunological or biochemical markers available that distinguish different ductal cell types of their precursors in the developing fetal and adult pancreas. The studies proposed herein may identify molecular markers of differentiation for these cells. The general goal of the project described in this application is to use contemporary techniques of primary cell culture, molecular biology and biochemistry to identify and characterize gene products that are involved in the development of differentiated pancreatic ductal cell function in humans. to accomplish this we will: 1) Generate cDNA libraries from freshly isolated adult human ducts or primary cultures, generate subtracted cDNA libraries between these and fetal pancreatic cells of different developmental ages, and then identify differentially expressed cDNAs using subtracted cDNA probes or a differential probe hybridization strategy; and 2) Characterize the adult and fetal ductal cells for expression of known and important products, and also for the new cDNAs derived in the studies described above (using antibodies and cDNA probes). It is possible that some genes involved in developmental events in the fetal pancreas will also be identified.